Gelatinase A is found in various tissues and cells, and known especially as an enzyme which degrade type IV collagen in the process of cancer metastasis.
FIG. 2 is a schematic view of APP 770, whose amino acid sequence (SEQ. ID NO: 1) has already been identified as shown in FIG. 1.
In FIG. 2(A), represents the signal sequence from 1M (Met), and 6 represents the peptide which is an active minimum unit of a gelatinase A inhibitor. This unit, in which carbohydrate chains are bound at 2 positions as represented by 2 CHO moieties in this figure, is called as the glycosylated region.
In FIG. 2(A), domain 8 penetrates through the plasma membrane of a cell.
In a normal cleavage process, APP is cleaved at the position designated by the arrow in the part of D in (A) of FIG. 2, i.e., in the amino acid sequence of (D) of FIG. 2. When D is not cleaved but closed and domain 7 is cut out at the both ends of the entire solid part as shown in the figure, the entire domain 7 is released as beta-amyloid (.beta.AP). Then the .beta.-amyloid deposits around neurons, and the neurons are degenerated and undergo atrophy, resulting in Alzheimer's disease.
As mentioned above, development of Alzheimer's disease is suspected to depend on the position at which domain 7 of APP is cut, i.e., the center or the both ends. At least, it is found in the present invention that gelatinase A is involved in the cut at the position designated by the arrow in (D).
Gelatinase A is known also as one of the matrix metalloproteinases secreted by cancer cells and the like.
Gelatinase A is also suspected to promote local destruction of the tissues which occurs in the process of infiltration and metastasis of cancer or to promote migration of leukocytes during inflammation. Thus, it is expected that inhibition or suppression of the activity of gelatinase A may ameliorate of the diseases.
It has never been known that gelatinase A can degrade .beta.-amyloid protein or that the activity of gelatinase A is inhibited or suppressed by APP or degradation products thereof.